Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


Type 2 diabetes (T2D) is characterized by insulin resistance and impaired insulin secretion, but the mechanisms underlying insulin secretion failure are not completely understood. Here, we show that a set of co-expressed genes, which is enriched for genes with islet-selective open chromatin, is associated with T2D. These genes are perturbed in T2D and have a similar expression pattern to that of dedifferentiated islets. We identify Sox5 as a regulator of the module. Sox5 knockdown induces gene expression changes similar to those observed in T2D and diabetic animals and has profound effects on insulin secretion, including reduced depolarization-evoked Ca(2+)-influx and β-cell exocytosis. SOX5 overexpression reverses the expression perturbations observed in a mouse model of T2D, increases the expression of key β-cell genes and improves glucose-stimulated insulin secretion in human islets from donors with T2D. We suggest that human islets in T2D display changes reminiscent of dedifferentiation and highlight SOX5 as a regulator of β-cell phenotype and function.


  • Annika Axelsson
  • T Mahdi
  • H A Nenonen
  • S Hänzelmann
  • Annika Bagge
  • T M Reinbothe
  • J Millstein
  • X Yang
  • B. Zhang
  • E G Gusmao
  • L Shu
  • M Szabat
  • Y Tang
  • Jinling Wang
  • Sofia Salö
  • J M J Derry
  • B Mecham
  • Ivan G Costa
  • A H Rosengren
Enheter & grupper
Externa organisationer
  • Hawler Medical University
  • Sage Bionetworks
  • University Medical Center, Geneva
  • Trialomics
  • RWTH Aachen University
  • University of California, Los Angeles
  • Göteborgs universitet
  • University of British Columbia
  • Lund University
  • Tianjin Medical University
  • Icahn School of Medicine at Mount Sinai
  • Xiamen University

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Endokrinologi och diabetes


Sidor (från-till)15652
TidskriftNature Communications
StatusPublished - 2017 jun 6
Peer review utfördJa